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Expert Panel Advises FDA Approve Qnexa for Obesity Treatment



Yesterday, the US FDA Endocrinologic and Metabolic Drugs Advisory Committee voted 20 to 2 in favour of approving Qnexa, a low-dose controlled-release formulation of phentermine and topiratmate, for the medical treatment of obesity.

This is the first positive vote for a new anti-obesity drug by the FDA committee in 13 years.

As I pointed out in my presentation (on behalf of the sponsor) to the Advisory Committee , Qnexa has the potential to address an important unmet clinical need – both the degree of weight loss (just over 10% on average) and the favourable trends in cardiovascular risk factors (with the exception of heart rate) have the potential of making this a significant advance in our ability to medically manage obesity.

As I told the Committee,

“Back in medical school, I was taught that when the risk of not treating a condition exceeds the risk of treating, then you treat.”

As readers of these pages know, there are indeed substantial health risks with not treating obesity in those who have evident obesity related health problems.

Not that there are no risks with treatment – based on the experience with the use of topiramate as an anti-epileptic drug and for the prevention of migraines, there is a likelihood that the topiratmate component in Qnexa (although contained at a lower dose) can increase the risk of orofacial clefts if taken during the first trimester of pregnancy – this is why, it is likely that the drug will not be freely available and there will be strict measures in place to minimize exposure in women, who may become pregnant. (discussion around this issue included a rather funny moment, when one of the panel members, asked how often you could expect the average ‘Joe’ to take a pregnancy test – this was quickly corrected to average ‘Jane’)

But there are also other risks like kidney stones, tingling in hands and feet, and perhaps some psychiatric issues that may need to be carefully monitored.

In this context it is important to remember, that at the recommended dose, Qnexa contains only about a quarter of the maximum dose of phentermine (30 mg) and less than one-eight of the maximum dose of topiramate (400 mg). The lower risk for side effects with these substantially lower doses is additionally mitigated by the controlled-release formulation.

This is probably why many of the common ‘side effects’ commonly associated with topiramate (e.g. memory and attention problems), were not a major issue in the Phase III studies. rather trial participants reported significant improvement in all aspects of quality of life, including physical functioning, self-esteem, sexual life, public distress, and work.

Obviously, it is important to remember that all participants in these trials (including those in the placebo group) also received comprehensive lifestyle education together with a 500 kcal calorie reduction.

While Qnexa is unlikely to work for everyone (there were about 25% non-responders in the trials), for patients who respond and tolerate this drug well, it may be a substantial step forward in managing their excess weight.

The strong positive vote of the Advisory Committee is not binding to the FDA, but it is highly likely, that the drug will eventually be approved.

It will certainly be most interesting to see how these benefits in clinical trials will translate into clinical practice once Qnexa hits the market.

AMS
Washington, DC

Disclaimer: I am a consultant to Vivus Inc, the maker of Qnexa

7 Comments

  1. How exactly does a drug which results in a weight loss of 10% of body weight, thus not moving those presumed to be at most risk out of the obese category, and which weight loss almost certainly cannot be maintained without remaining on the drug, if even then, actually help anyone? Are there not non- medical treatments such as exercise which could achieve cardiac and other benefits without the risks of this drug? It seems to me that the biggest beneficiary of it would be Vivus.

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  2. Any thoughts on how to prevent weight loss drugs from being prescribed off-label? I’m not sure if this is the case or not, but I was under the impression that Rimonabant was probably a useful drug if prescribed appropriately, but when prescribed too widely to patients who weren’t a good fit for the drug, the number of side effects were just too high. It seems like that is a likely situation for any obesity drug, given the number of individuals who would like to lose weight.

    Am I off base in that assumption? If not, how do physicians ensure that future weight loss drugs will be prescribed appropriately so as not to be removed from the market down the road?

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  3. How long term and large were the studies reported to the panel? Who pays for all the necessary monitoring — Vivius, governments or patients? How real time and unbiased is the monitoring? Was the pressure for a new obesity treatment drug (none since 1999)an issue in the panel’s judgement? Please inform and expand in follow-up blogs.

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  4. The easy approval of drugs like this, drugs that carry very serious health risks and risks that last long after stopping the drugs (up to a year after stopping the drug a woman is more likely to have a baby with birth defects that result from the drug) if the goal in anti-obesity medicine is to eliminate obesity by killing off the fatties through one treatment or another.

    I have to wonder whether you’d heap such praise on such a risk laden drug that has such low reward if you were not paid to do so.

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  5. What a disappointment. I can only echo the excellent comments of Cheryl Fuller found above.

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  6. “Back in medical school, I was taught that when the risk of not treating a condition exceeds the risk of treating, then you treat.”

    Please explain to me how having a BMI of 30 with NO co-morbidities is a case where not treating is riskier than treating. So in other words, if I’m active, eating a good diet, perfectly healthy but “too big” according to the charts, this would be acceptable.

    Please explain what the bar is for “co-morbidities” that will permit prescribing this down to BMI 27 — especially since those seem to keep being defined downward (what was once “normal” blood pressure is now “pre-hypertensive.”)

    I predict that this will not be prescribed only to people facing serious health issues where an any means necessary approach might be justified. It will be advertised constantly on every TV station, sandwiched between the viagra and cialis ads, and prescribed to people who will get no real benefit but will be harmed by the side effects.

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  7. Yeah, it’s tough to see how getting a BMI of 30 down to 27 has enough payoff to deal with side effects of a lifetime on the Barbie Doll Drug. I think some of the problems in the line of thinking of treating BMI of 30 to 27 are similar to the line of thinking of recent HDL drugs. In other words, high HDL correlates with good health, so let’s make a drug that increases HDL and it will increase health.

    Sadly, since correlation does not imply causation, torcetrapib went down in flames. I think we are seeing the same thing, BMI correlates to good outcomes, because BMI correlates to body fat percentage, and body fat percentages in a good range correlate to healthier eating and more activity than those whose body fats are high.

    I’m convinced moving more and eating less processed food will make you healthier even if it doesn’t drop your BMI, and I suspect it will drop your BMI. I’m not convinced eating the same crap and not moving much but taking Qnexa will make you healthier, even if you drop your BMI.

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